The principal objective of the research is to obtain quantitative data on dose response relationships for the induction of mutations in an in vitro mammalian cell system. Chinese hamster ovary (CHO) cells are selected for their resistance to 8-azaguanine, a toxic analogue which selects for a mutation in the gene for hypoxanthine-guanine phosphoribosyl transferase. Factors which influence the quantitative nature of the mutation response such as drug concentration, cell density, and expression time, are carefully controlled to obtain accurate induction measurements. The mutation induction by x-rays is being determined for different stages of the cell cycle, several dose-rates, and various hyperfractionation schedules. The influence of the repair of sublethal and potentially lethal mutation lesions on the total induction is being quantified. The possible influence of hyperthermia on mutation production is being investigated. An analysis of mutants selected under several irradiation and growth conditions will be aimed at determining the nature of the mutation lesion.